There have been a number of studies concerning the possible detrimental effects of marijuana on the immune response system, both in man and experimental animal. With the continued widespread use of marijuana and the potential widespread use of this agent in therapy for cancer patients, it is obviously important to understand whether marijuana and other cannabinoid preparations affect the immune response mechanisms, either in a negative or positive manner. It appears likely that psychopharmacologically active agents may influence immune responses. This has been shown recently with a number of neuropeptides and immunopeptides. The effects of marijuana on immume responses in a single laboratory study will be examined in the proposed study. The major goal is to examine in detail the influence of marijuana components on both humoral and cellular immune responses in vivo and in vitro. For this purpose the influence of tetrahydrocannabinol on antibody formation by murine splenocytes from mice immunized with sheep erythrocytes, a T-cell dependent antigen, or E. coli lipopolysaccharide, a T-cell independent antigen, will be determined utilizing single antibody plaque forming assays and immunoserologic procedures. The effects of tetrahydrocannibanol on the in vitro immune response, both primary and secondary, to the sheep red cells and E. coli antigen will also be determined in a completely in vitro model system using the plaque assays. In addition, the effects of THC on cell mediated immune responses will be determined, both in vivo and in vitro. Skin graft rejection responses and in vitro lymphocytes blastogenic responses to transplantation antigens, plant mitogens and microbial antigens will be determined. Effects of THC on lymphokine production in vitro and in vivo, assayed by cell-mediated immune response models, will be determined. Additional studies will be carried out to determine whether THC has an effect on the functional activity of macrophages, either in the spleen, the peritoneum or in the lung. The phagocytic function of macrophages, including the ability to ingest test particles and neutralize or inhibit bacteria, such as staphylococci and E. coli, will be determined, as well as the ability to neutralize an upper respiratory viral pathogen, i.e., influenza. By these studies it will be possible to determine in a single multifaceted experimental model system whether THC has a definitive effect in vitro and/or in vivo on either humoral or cellular immune response mechanisms, or both.